To understand the molecular mechanism of Leishmania pathogenesis, we are analyzing the processes that are involved in parasite development/differentiation from an avirulent to virulent form. We argued that the phenotypic changes that occur during parasite transformation are controlled by the changes in the genotypic expression. As a first step towards that we have identified several genes of L. donovani that are differentially regulated during parasite differentiation using several molecular biology techniques. We characterized some of these genes by determining their nucleotide sequence and mRNA expression at various stages of parasite life cycle. In order to determine the biological function of the differentially regulated genes in the parasite pathogenesis we are now altering their expression in Leishmania by gene- knock out experiments. Mutant parasite with altered infectivity could be developed into a live attenuated Leishmania Vaccine.